The overall objective of this study is to further our understanding of cardiac autorhythmicity by investigating electrogenesis in single cardiac pacemaker cells. Recent and conflicting evidence points to the need for a unifying theory linking calcium to mechanisms of cardiac automaticity. The proposed investigation intends to examine this relationship with respect to latent pacemaker cells, i.e., ventricular Purkinje fibers. Specific studies are designed to test the hypothesis that intracellular calcium plays an important role in the beat-to-beat modulation of the potassium current involved in pacemaker activitiy. Rapid electrical stimulation, ionophoretic injection technique and the application of agents such as catecholamines, ryanodine, manganese, and verapamil will be employed to alter intracellular calcium concentration. Membrane potential and membrane cable properties will be determined as a function of these experimental procedures.